Integration of miRNA and gene expression profiles suggest a role for miRNAs in the pathobiological processes of acute Trypanosoma cruzi infection

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Pinto Ferreira, Ludmila Rodrigues ^{[1, 2, 3, 4]} ; Ferreira, Frederico Moraes ^{[3, 4]} ; Laugier, Laurie ^[5] ; Cabantous, Sandrine ^[5] ; Navarro, Isabela Cunha ^{[1, 3, 4]} ; Candido, Darlan da Silva ^{[1, 3, 4]} ; Rigaud, Vagner Carvalho ^{[1, 3, 4]} ; Real, Juliana Monte ^{[6, 7]} ; Pereira, Glaucia Vilar ^[8] ; Pereira, Isabela Resende ^[8] ; Ruivo, Leonardo ^[8] ; Pandey, Ramendra Pati ^{[1, 3, 4]} ; Savoia, Marilda ^{[1, 3, 4]} ; Kalil, Jorge ^{[1, 3, 4]} ; Lannes-Vieira, Joseli ^[8] ; Nakaya, Helder ^{[9, 10]} ; Chevillard, Christophe ^{[5, 11]} ; Cunha-Neto, Edecio ^{[1, 3, 4]}

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^[1] Univ Sao Paulo, Sch Med, Div Clin Immunol & Allergy, Sao Paulo - Brazil

^[2] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Morfol, Belo Horizonte, MG - Brazil

^[3] Univ Sao Paulo, Sch Med, Heart Inst InCor, Lab Immunol, Sao Paulo - Brazil

^[4] Iii INCT, Inst Invest Immunol, Sao Paulo - Brazil

^[5] Aix Marseille Univ, INSERM, Fac Med, U1108, Marseille - France

^[6] Santa Marcelina Hosp, Dept Pediat Oncol, TUCCA Assoc Children & Adolescents Canc, Sao Paulo - Brazil

^[7] Univ Sao Paulo, Inst Canc Estado Sao Paulo, Ctr Invest Translac Oncol, Sao Paulo - Brazil

^[8] Fiocruz MS, Oswaldo Cruz Inst, Lab Biol Interact, Rio De Janeiro - Brazil

^[9] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Pathophysiol & Toxicol, BR-077010 Sao Paulo - Brazil

^[10] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 - USA

^[11] Aix Marseille Univ, UMR1090, INSERM, Parc Sci Luminy Case 928, 163 Ave Luminy, Marseille - France

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 7, DEC 21 2017.
• Citações Web of Science: 4

Resumo

Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America. Its acute phase is associated with high parasitism, myocarditis and profound myocardial gene expression changes. A chronic phase ensues where 30% develop severe heart lesions. Mouse models of T. cruzi infection have been used to study heart damage in Chagas disease. The aim of this study was to provide an interactome between miRNAs and their targetome in Chagas heart disease by integrating gene and microRNA expression profiling data from hearts of T. cruzi infected mice. Gene expression profiling revealed enrichment in biological processes and pathways associated with immune response and metabolism. Pathways, functional and upstream regulator analysis of the intersections between predicted targets of differentially expressed microRNAs and differentially expressed mRNAs revealed enrichment in biological processes and pathways such as IFN gamma, TNF alpha, NF-kappa B signaling signatures, CTL-mediated apoptosis, mitochondrial dysfunction, and Nrf2-modulated antioxidative responses. We also observed enrichment in other key heart disease-related processes like myocarditis, fibrosis, hypertrophy and arrhythmia. Our correlation study suggests that miRNAs may be implicated in the pathophysiological processes taking place the hearts of acutely T. cruzi-infected mice. (AU)

• Processo FAPESP: 13/50302-3 - Identificação de uma assinatura genética preditiva / prognóstica na Doença de Chagas: abordagem de biologia de sistemas
• Beneficiário: Edecio Cunha Neto
• Modalidade de apoio: Auxílio à Pesquisa - Regular